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Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties

机译：白细胞介素-27治疗的人巨噬细胞诱导新型微稻草的表达这可能介导抗病毒性质

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摘要

Interleukin-27 (IL-27) is a pleiotropic cytokine which plays important and diverse roles in the immune system. We have previously demonstrated that IL-27 induces potent anti-viral effects against HIV-1, HIV-2, SIV, HSV-2, KSHV and influenza viruses in macrophages. This induction occurred in an Interferon (IFN) independent manner and involved down regulation of SPTBN1. MicroRNAs (miRNAs) are critical regulators of mRNA translation and turnover. There have been reports that some miRNAs inhibit viral replication. In this study, we hypothesized that IL-27 could induce the expression of novel miRNAs in macrophages which may have functional relevance in terms of anti-viral activity and primary monocytes were differentiated into macrophages using either M-CSF (M-Mac) or a combination of M-CSF and IL-27 (I-Mac) for seven days. Following this, total RNA was extracted from these cells and deep sequencing was performed, in parallel with gene expression microarrays. Using the novel miRNA discovery software, miRDeep, seven novel miRNAs were discovered in these macrophages. Four of which were preferentially expressed in I-Mac (miR-SX1, -SX2, -SX3 and -SX6) whilst three were detected in both M-Mac and I-Mac (miR-SX4, -SX5 and -SX7). The expression of six of the seven novel miRNAs was highly correlated with qRT-PCR using specific primer/probes designed for the novel miRNAs. Gene expression microarray further demonstrated that a number of genes were potentially targeted by these differentially expressed novel miRNAs. Finally, several of these novel miRNAs (miR-SX1, -SX4, -SX5, -SX6 and -SX7) were shown to target the open reading frames of a number of viruses (including HSV-1, HSV-2 and HHV-8) which may partially explain the anti-viral properties observed.
机译：白介素27（IL-27）是一种多效细胞因子，在免疫系统中起着重要而多样的作用。先前我们已经证明IL-27在巨噬细胞中诱导针对HIV-1，HIV-2，SIV，HSV-2，KSHV和流感病毒的有效抗病毒作用。这种诱导以干扰素（IFN）独立的方式发生，并且涉及SPTBN1的下调。微小RNA（miRNA）是mRNA翻译和转换的关键调节剂。有报道说一些miRNA抑制病毒复制。在这项研究中，我们假设IL-27可以诱导巨噬细胞中新型miRNA的表达，这可能与抗病毒活性具有功能相关性，并且使用M-CSF（M-Mac）或巨噬细胞将原代单核细胞分化为巨噬细胞M-CSF和IL-27（I-Mac）联合治疗7天。之后，从这些细胞中提取总RNA，并与基因表达微阵列并行进行深度测序。使用新型miRNA发现软件miRDeep，在这些巨噬细胞中发现了七个新型miRNA。其中四个优先在I-Mac中表达（miR-SX1，-SX2，-SX3和-SX6），而三个在M-Mac和I-Mac中均被检测到（miR-SX4，-SX5和-SX7）。使用针对新型miRNA设计的特异性引物/探针，七个新型miRNA中的六种表达与qRT-PCR高度相关。基因表达微阵列进一步证明，这些差异表达的新型miRNA可能靶向许多基因。最后，这些新颖的miRNA中的几种（miR-SX1，-SX4，-SX5，-SX6和-SX7）显示出可靶向许多病毒（包括HSV-1，HSV-2和HHV-8）的开放阅读框）可以部分解释观察到的抗病毒特性。

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